The proposed research is designed to help elucidate the chemical mechanisms involved in learning and the formation of memory. The neurochemical effects of amnestic treatments such as electroconvulsive shock will be examined and attempts made to correlate such effects with the amnesia. Particular attention will be paid to an observed loss of glycoproteins and gangliosides at synapses which may also relate to electroconvulsive therapy. Previously untested antibiotic inhibitor of protein synthesis will be tested for their amnestic effects, and the suggested role of the adrenal gland in the amnesia investigated. Because of a suspected effect of ACTH on brain protein synthesis which occurs during the training of mice, and the reported behavioral effects of ACTH and related peptides, we will investigate the cerebral interactions of ACTH, ACTH analogs without adrenocortical activity, and also MSH and lysine vasopressin. Specifically we will study the effects of these hormones on protein synthesis, amino acid metabolism and catecholamine and serotonin metabolism. We will also attempt to localize the hormonal effects by autoradiographic and binding studies and by characterizing the receptors for ACTH and possibly other hormones. Possible interactions between the hormones, catecholamine neurotransmitters and protein synthesis will be investigated to evaluate proposed mechanisms for the hormonal action. We shall also investigate changes in cerebral blood flow and glucose uptake following administration of pituitary-adrenal hormones and during behavioral experiences. These analyses will be performed by radioisotopic techniques involving both scintillation counting and autoradiography.